ACTA ENDOCRINOLOGICA (BUC)

Introduction. Estrogens are known to have a neuroprotective role and to influence the permeability of the blood brain barrier (BBB). An ongoing debate exists on the changing effects of estrogens on target tissues with advancing age and at menopause and on the potential disruptive role of increasing gonadotropin levels.\r\nThe aim of the present study was to assess the permeability of the BBB for estradiol, FSH and LH in three physiological states: early follicular phase, preovulatory phase and at menopause.\r\nMethod. Hormonal levels were assessed simultaneously in the serum and cerebrospinal fluid (CSF) of 15 women at menopause (mean age 60?8 years), 16 of reproductive age in early follicular phase and 11 in preovulatory phase (mean age 31?7 years), all undergoing surgery for benign gynecologic disorders. FSH, LH and estradiol levels were assessed using chemo luminescence and are expressed as median and 10-90 percentile interval. Statistical analysis assessed the serum-CSF correlation and the CSF/serum ratio for each hormone between groups.\r\nResults. Estradiol serum levels were 26.2 pg/ml (6.4-43.5) at menopause (n=15), 58.5 pg/ml (25.7-75.9) in early follicular phase (EFP, n=16) and 221.2 pg/ml (113.7-405.5) in preovulatory phase (PREOV, n=11). CSF estradiol is 18.5 pg/ml (0.4-30.5) at menopause, 5.4 pg/ml (2.2-10.2) in EFP (p<0.001) and 17.3 pg/ml (10.3-34.6) in PREOV patients. Estradiol serum and CSF levels correlate positively in the fertile cycle (r=0.72, p<0.0001) and negatively at menopause (r=-0.88, p<0.05). The CSF/serum ratio for estradiol is 0.8 (0.01-4.4) at menopause, 0.1 (0.04-0.13) in EFP and 0.1 (0.03-0.13) in PREOV patients. FSH serum levels were 75.8 mUI/ml (35.9-129.8) at menopause, 7.7 mUI/ml (3.5-11.4) in EFP and 7.3 mUI/ml (3.1-10.7) in PREOV patients. CSF FSH is 2.7 mUI/ml (0.4- 5.9) at menopause, significantly higher than 0.7 mUI/ml (0.3-1) in EFP (p<0.001) and 0.5 mUI/ml (0.2-1) in PREOV patients (p<0.05). FSH serum and CSF levels correlate positively in the fertile cycle (r=0.8, p<0.0001) and do not correlate at menopause (p=NS). The CSF/serum ratio for FSH is 0.03 (0.01-0.1) at menopause, significantly lower than 0.09 (0.06-0.16) in EFP (p<0.001) and is 0.06 (0.03-0.13) in PREOV phase. LH serum levels were 57.4 mUI/ml (27.5-84.8) at menopause, 4.7 mUI/ml (1.7-7.1) in EFP and 5.5 mUI/ml (4.9-8.02) in PREOV phase. CSF LH is 1.6 mUI/ml (0.7-2.6) at menopause, significantly higher than 0.4 mUI/ml (0.1-1) in EFP (p<0.001) and 0.5 mUI/ml (0.2-0.9) in preovulatory phase (p<0.05). The CSF/serum ratio for LH is 0.03 (0.01-0.07) at menopause, it is significantly lower than 0.09 (0.03-0.27) in EFP (p<0.001) and is 0.07 (0.03-0.14) in preovulatory phase.\r\nConclusions. This study shows the negative correlation of serum and CSF estradiol levels at menopause reflecting the need of constant estrogen levels within the CSF despite low chronic serum levels. Simultaneously, the CSF/serum ratio for gonadotrophins is\r\nreduced significantly at menopause and the positive correlation of serum and CSF levels is lost, reflecting a protective mechanism against rising levels of FSH and LH.

Objectives. The purpose of this study was to evaluate the association between the follicle-stimulating hormone (FSH) receptor (c.-29G>A) and FSH beta chain (c.- 280G>T) polymorphisms and endometriosis in Romanian women. Material and methods. We performed the polymorphic analysis of the FSH receptor gene and FSH beta chain in 44 patients with endometriosis and 34 controls. Genomic DNA was obtained from peripheral blood and polymorphisms were investigated using restriction fragment length polymorphism analysis (RFLP). Results. There were no significant differences in genotype frequencies of FSH receptor gene between endometriosis patients and controls. For the heterozygous type of the FSH receptor polymorphism (c.-29G>A) we did not find a significant difference in its frequency between patients with minimal/mild and moderate/severe endometriosis (p = 0.136). Also, the FSH beta chain (c.- 280G> T) polymorphism frequency was not significantly associated with the severity of endometriosis (p = 0.966). Conclusions. FSH receptor and FSH beta chain polymorphisms do not seem to influence the severity of endometriosis, but they could be correlated with female infertility (primary or secondary), therefore further studies are required to debate this topic.

Purpose. To determine the effectiveness of the basal calcitonin (CTb) determination in the early postoperative period to predict the possible recurrence (persistence) of medullary thyroid cancer (MTC). Material and Methods. A retrospective study of the treatment results in 194 patients with MTC (148 (76.3%) primary – group 1 and 46 (23.8%) recurrent – group 2) according to the levels of CTb in the first week after surgery and one year later. All groups were analyzed by staging, the level of preoperative and postoperative basal calcitonin 5 days and 1 year after the primary surgery. Findings. Among all patients, women prevailed – 144 (74.2%), the average age was (48.7±15.2), the average follow-up period was 67.5 months. Basal calcitonin was studied in patients of all groups in the preoperative and serially in the postoperative periods: 5 days and 1 year after the most radical surgical volumes. To test the hypothesis about the possibility of using CTb indicators in the early postoperative period, the degree of compliance with normal calcitonin indicators (≤18 pg/mL) was assessed by observation groups 5 days and 1 year after surgery. Conclusions. 1. The CTb value 5 days after surgery is no less a reliable marker of the result of surgical treatment of MTC than the currently recommended CTb measurement 2-3 months after surgery. 2. The technique is applicable for both primary and reoperations used for recurrent forms of medullary thyroid cancer.

Parathyroid imaging modalities have been used to guide clinicians and surgeons in finding the source of hyperparathyroidism for over 40 years. Primary hyperparathyroidism (PHPT) is generally caused by a parathyroid gland(s) autonomous production of parathyroid hormone (PTH), associated by enlargement of one or more glands. Noninvasive imaging procedures that are used in the management of hyperparathyroidism are anatomical (ultrasound, computer tomography, magnetic resonance imaging) and/or functional (nuclear medicine techniques: planar scintigraphy, single photon emission tomography, positron emission imaging) and/or hybrid imaging.

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IGF-I (Insulin like growth factor-I) plays a definitive role in the central nervous system (CNS) by modulating neuronal regeneration and survival. The local production of IGF-I in CNS has been demonstrated, but the contribution of circulating IGF-I transported through blood-brain barrier (BBB) has been just suggested in animals. There is currently no data available concerning IGF-I transport in CNS in humans. In order to investigate the passage of IGF-I over BBB in humans we have simultaneously measured the IGF-I and GH levels in serum and CSF in 25 patients with active acromegaly. IGF-I and GH levels in CSF were lower than in serum (2.2 ? 0.24 ng/mL vs 686.6 ? 46.83 ng/mL for IGF-I and 2.13 ? 0.627 mU/l vs 58.8 ? 15.86 mU/L for GH). However, both IGF-I and GH serum levels correlated with their CSF levels (r= 0.4, p<0.05 for IGF-I and r= 0.651, p= 0.006 for GH), suggesting that BBB is permeable for both hormones. In conclusion, we demonstrate the correlation of the IGF-I levels in serum and CSF, providing indirect evidence for IGF-I passage through BBB.

In response to increasing interest of the European Commission on large-scale\r\ngenotyping for complex diseases, including variability in ethnic minorities in\r\nEurope (HEALTH-2009-4.3.3-1), at the end of 2008 we composed the\r\nHAPLOGENDIS consortium with partners from Russia and European countries. A\r\nfirst program (SICA) was proposed in cooperation with Russian Federal Agency for\r\nScience and Innovation, focusing on comparative population genetics on diseases\r\naccompanied by insulin resistance. Beside the specificity in analyzing the human\r\ngenome with SNP (single nucleotide polymorphism) and defining haplotype\r\nstructure of genes, the program rises new hypotheses which directly link\r\ncolonization of Europe at the Neolithic period from Eastern Ukraine or Anatolia\r\nwith the development of agriculture and major dietary and life style changes that\r\nmay have an impact on the genome. Although there will be many occasions to\r\nreview both genetic and clinical detailed aspects, this short note will expose some\r\nunifying ideas that joint these partners.

Background. Our study outlines the implication of melatonin in organisms' pain regulatory mechanisms. The literature describes epiphysis opioidergic fibers with µ and d opioid receptors and also pleads for an analgesic dose-dependent effect of melatonin. We analyzed the biologic variability of the analgesic effect of the pineal hormone, based on the psychoneuroendocrine behavior type. In our previous studies we investigated the dinamics of melatonin's analgesic effect within the following psychoneuroendocrine behavioral types: the adrenergic type (hipersensitive to pain), the opioid type (pain hyporeactive) and the intermediate, equilibrated typology (N type). Objectives. Our present research focused on the antinociceptive pharmacologic psychoneuroendocrine variability in the case of co-administration of melatonin (50mg/kgbw, i.p.) with ondansetron (4 mg/kgbw, i.p.), petidine (4mg/kgbw, i.p.) and tramadol (4mg/kgbw, i.p.). Subjects and Methods. Experiments were performed in vivo, using Albino Swiss male mice. Pain sensitivity was assessed using the classical pharmacologic test hot-plate (60°C). Conclusions. Our results showed an amplification of the analgesic effect when petidine was co-administered with melatonin, with best results for the A type of behavior (p<0.02), as follows: 63.41% (melatonin + petidine co-administration) > 54.54% (melatonin + tramadol coadministration) ≈ 52% (melatonin). We also noticed an antagonism between ondansetron and the pineal biomolecule

Phenylketonuria (PKU) is the most frequent inherited amino acid metabolic disorder, and it may also be treated by dietary means. The determination of phenylalanine (Phe) levels in the blood plasma is important not only in early diagnostic, but also in monitoring the treatment of PKU. Purpose. The aim of our work was to develop a simple, sensitive and highly accurate procedure to determine the plasma concentration of Phe. Procedure. The measurement of plasma Phe concentration involves two steps: a) separation of plasma (from the blood taken on heparin), isolation and preparation of a concentrated solution of amino acids (by ion-exchange column chromatography on Dowex-50X8 and evaporation of the eluate in vacuum at 40˚C), and b) determination of Phe concentration in the solution of amino acids by HPLC. This analysis was performed using a Dionex Ultimate 3000 instrument equipped with a Ultimate 3000 diode array detector (DAD). The values of Phe concentration in the plasma of several patients were calculated using a calibration curve made with standards of Phe (dilutions of a stock solution of 50 mg/ dL). The measurements in duplicate (plasma Phe) or a greater number of samples from the same concentration of standards of Phe showed extremely small sample to sample differences. Concentrations as low as 0.2 mg/dL could be determined. Conclusion. The whole procedure presented here is relatively simple, rather inexpensive, however very sensitive and highly accurate. Consequently, it is very adequate for confirming the diagnosis of PKU in patients with neonatal hyperphenylalaninemia, as well as for monitoring the plasma concentration of Phe in patients with PKU.

Testosterone influences cancer development. This in vitro experiment was exerted to determine the association of testosterone with human colorectal cancer(HT29), glioblastoma (A172) and human embryonic kidney(HEK293) cells proliferation. HT-29, A172 and HEK293 cell lines were cultured in standard growth medium, then randomly divided into control group (not exposed to testosterone) and groups exposed to 1, 10, 100 and 1000 μg/mL of testosterone. Cell viability was quantified by MTT assay. Statistical analysis was performed using ANOVA. Viability of HEK293 cells significantly increased in groups exposed to 1 μg/mL and decreased in groups exposed to 100 and 1000 μg/mL of testosterone compared to control group (P<0.05, P<0.05 and P<0.001, respectively). Viability of HT29 cells significantly increased in groups exposed to 10 and 100 μg/mL of testosterone and significantly decreased when exposed to 1000 μg/mL of testosterone compared to control group (P<0.05, P<0.001 and P<0.001, respectively). Viability of A172 cells significantly decreased in groups exposed to 100 and 1000 μg/mL of testosterone compared to control group (P<0.001). In conclusion, different doses of testosterone have enhancing or suppressive effects on HEK293, HT29 and A172 cells proliferation; according to which, considering clinical use of testosterone therapy for cancer treatment is a highly controversial issue.